Series A Round sets Otologic Pharmaceuticals hearing-loss pill on path to the clinic

By Randy OsborneStaff Writer

Otologic Pharmaceutics Inc.’s $4.1 million in series A funding will help the Oklahoma City-based firm start a phase I trial this year with NHPN-1010, an oral combo therapy designed to reverse noise-induced hearing loss.

“The military is interested because NIHL is their number-one expense for disability,” said Clayton Duncan, chairman and CEO of the aptly named Oklahoma City-based biotech accelerator Accele Biopharma Inc., the investing arm of which put the new money into 2009-founded Otologic. Also contributing was the Oklahoma Life Science Fund contributed.

About $1.5 billion per year is spent by the armed forces on NIHL, Duncan said. “You’ve got aircraft carriers with noise, and artillery, and you just can’t block it all out,” he said, noting that, if the compound works, it could also find use in traumatic hearing loss due to heavy machinery noise in construction and manufacturing – an orphan indication.

“The initial insult, the initial blast or high-frequency noise, causes damage, and it’s temporary at first,” Duncan said. “With [NHPN-1010], it seems the ear can repair itself, and the damaged nerve cells can recover. If they don’t, then you end up with a hearing aid.”

NHPN-1010 is a combination of known therapies HPN-07 (2,4-disulfonyl α-phenyl tertiary butyl nitrone) and N-acetylcysteine (NAC). The latter is approved for intravenous use in liver toxicity (such as can be caused by acetaminophen).

“It’s been tested a lot in a lot of situations,” Duncan said, including a 300-patient hearing loss trial conducted by the military with firing-range patients. “There were some interesting trends, and we got close,” he said. “If they were right-handed shooters, it made a difference in the right ear vs. left ear.”

HPN-07, the second ingredient of NHPN-1010, is “a very potent antioxidant, and it has some other mechanisms,” Duncan said. London-based Astrazeneca plc tested the compound in stroke, missing the endpoint in phase III trials. “It’s been in about 3,000 patients and looks pretty safe,” he said.

The next indication in which NHPN-1010 will be tried is hearing loss caused by toxicity, a much larger patient population. This year, the firm will start investigational new drug application-enabling studies to support experiments with the drug in preventing or reversing acute cisplatin-induced hearing loss. Cisplatin causes significant hearing loss in more than 75 percent of the nearly 700,000 patients treated each year.

“We’re exploring preclinical models at this point,” Duncan told BioWorld Today. “From what I know of the mechanisms, it should work.”

Otologic and its collaborators, the Hough Ear Institute and the Oklahoma Medical Research Foundation, also plan to test NHPN-1010 in tinnitus, vestibular injury and traumatic brain injury-associated hearing disorders.

Duncan rattled off the firms doing research in Otologic’s area. Auris Medical AG, of Basel, Switzerland, has a phase II-stage compound for hearing loss that involves an injection through the tympanic membrane. Auris caused players in the space to sit up straight last year with a series C round of $51 million to boost its N-Methyl-D-aspartate receptor antagonist in tinnitus, along with the peptide-based blocker of c-Jun N-terminal kinase signaling for hearing loss. (See BioWorld Today, April 17, 2013.)

San Diego-based Otonomy Inc. is pursuing, at the preclinical level, a method of similarly directed drug delivery of dexamethasone. Sound Pharmaceuticals Inc., of Seattle, has ebeslen (also known as SPI-1005), a glutathione mimic and antioxidant, at the phase II stage for NIHL due to long-term exposure to noise, such as iPods and inserted ear buds. Otonomy also scored a hefty series C in 2013, gaining $45.9 million in a round led by Orbimed Advisors LLC. (See BioWorld Today, Sept. 5, 2013.)

This year, Indianapolis-based Eli Lilly and Co. entered the hearing loss arena by investing in a series A round for Audion Therapeutics BV, of Amsterdam, and providing a series of compounds, including its γ-secretase inhibitors, to test their potential in hair cell regeneration. (See BioWorld Today, Feb. 11, 2014.)

Also conducting research that is related but not directly competitive to Otologic are London-based Autifony Therapeutics Ltd., which is focused on age-related hearing loss, exploiting potassium channels to improve cognitive ability to understand signals from the ear, and Genvec Inc., of Gaithersburg, Md., which is trying RNAi therapies to restore hearing loss.

In connection with Otologic’s series A, Duncan has been appointed as the company’s CEO, replacing David Karlman in this position. Other members of the team include Richard Gammans, also of Accele Biopharma and recently appointed to the newly created positions of Otologic’s chief operating officer and head of research and development; Otologic’s co-founder and chief medical officer, Richard Kopke; co-founder and chief science officer Robert Floyd; and Kelle Jones, vice president of finance.